CN107814814A - A kind of D50 is the preparation method of 26 48 microns of bromocriptine methanesulfonate - Google Patents
A kind of D50 is the preparation method of 26 48 microns of bromocriptine methanesulfonate Download PDFInfo
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- CN107814814A CN107814814A CN201711170575.8A CN201711170575A CN107814814A CN 107814814 A CN107814814 A CN 107814814A CN 201711170575 A CN201711170575 A CN 201711170575A CN 107814814 A CN107814814 A CN 107814814A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
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Abstract
The present invention relates to a kind of process for purification of bromocriptine methanesulfonate, belong to chemosynthesis technical field.The technical scheme is that bromocriptine methanesulfonate dissolving crude product first in absolute ethyl alcohol, adds activated carbon, stir 12 hours, filtering；The mixed solution of ethanol and acetone is slowly added dropwise into filtrate；Solution is cooled to 8 DEG C to 0 DEG C and kept, 50% ethanol water of first step solvent volume 5 10% is added into solution, continues stirring 24 hours, is kept stirring for 50 55 turns per minute of speed；Filtering, 35 DEG C are dried in vacuo, and obtain the bromocriptine methanesulfonate bulk drug of suitable imitation medicine Conformance Assessment of the present invention.
Description
Technical field
The present invention relates to a kind of process for purification of bromocriptine methanesulfonate, belong to chemosynthesis technical field.
Background technology
Bromocriptine methanesulfonate piece also known as bromocriptine parlodel, it is polyamine form, being capable of Hypothalamic Stimulation release skin
A variety of hormones such as matter alcohol, growth hormone, prolactin(PRL, promote the biological clock of body to recover the normal rhythm and pace of moving things, be used to treat pa earliest
The gloomy syndrome of gold, the dysfunction of acromegalia and hyperprolactinemia correlation, by the research and development of Novartis companies of Switzerland simultaneously
Listed in 1976.Pharmacological action of the Ergo Science companies to bromocriptine methanesulfonate develops first after carrying out follow-up study
The oral quick release piece of sulfonic acid bromocriptine, it can be controlled on central nervous system level by adjusting the biochemical exception of cerebral nerve
Postprandial blood sugar, improve insulin resistance, so as to for treating II patients with type Ⅰ DM.This product in November, 2010 in the U.S. first
Listing.
Bromocriptine methanesulfonate is not soluble in water, to meet the dissolution specification of States Pharmacopoeia specifications, and imitation medicine Conformance Assessment
It is required that, it is necessary to use the bromocriptine methanesulfonate that D50 is 26-48 microns.Using grinding mode obtain needed for granularity, mechanical shock
Relevant material is easily caused to raise.
The content of the invention
Goal of the invention：It is an object of the invention to provide the bromocriptine methanesulfonate bulk drug that a kind of D50 is 26-48 microns, it is
Preparation, which provides, directly to be applied, and does not need the bulk drug of specially treated.
Technical scheme：
The technical scheme is that：A kind of D50 is the preparation method of the bromocriptine methanesulfonate of 26-48 microns, including following steps
Suddenly：
First step bromocriptine methanesulfonate dissolving crude product adds activated carbon in absolute ethyl alcohol, stirs 1-2 hours, filters, and retains
Filtrate；
The preferable technical scheme of this step, resulting solution concentration are 8-16%（Mass volume ratio）.
The preferable technical scheme of this step, the amount for adding activated carbon is the 8-10% of bromocriptine methanesulfonate crude product amount.
Under second step stirring, the mixed solution of ethanol and acetone is slowly added dropwise into filtrate, the amount that mixed solution is added dropwise is
First step quantity of solvent 30-60%；
In the mixed solution of the preferable technical scheme of this step, ethanol and acetone, the volume ratio of ethanol and acetone is（1-3）:1.
The preferable technical scheme of this step, the amount for adding mixed solvent is the 38-54% of first step quantity of solvent.
Under the stirring of 3rd step, solution is cooled to 10 DEG C with 5 DEG C of the speed of cooling per hour and kept, it is small to continue stirring 1
When；
4th step continues that solution is cooled into -8 DEG C to 0 DEG C with 5 DEG C of the speed of per hour cooling and kept, and is added into solution
First step solvent volume 5-10% 50% ethanol water, continue to stir 2-4 hours, be kept stirring for speed 50-55 per minute and turn；
The preferable technical scheme of this step, the volume for adding ethanol water are the 8% of first step quantity of solvent.
5th step is filtered, and filter cake is washed with 50% ethanol water, and filter cake is spread out, in 35 DEG C of vacuum drying.
Beneficial effect：The invention provides the bromocriptine methanesulfonate bulk drug that D50 is 26-48 microns, provided for preparation
Specially treated is not needed, the bulk drug directly used.The present invention obtains bromocriptine methanesulfonate, disclosure satisfy that Conformance Assessment pair
The requirement of bulk drug.Using the tablet prepared by bromocriptine methanesulfonate of the present invention, in the patent of Application No. 2017111691257
It is on the books in application.This is simple for process, is adapted to industrialized production.
The embodiment of the present invention is prepared with crude product by prior art, and high performance liquid chromatography detection purity is 95.92%.
Embodiment 1, first step 8g bromocriptine methanesulfonates crude product solution add 0.64g activity in 100ml absolute ethyl alcohols
Charcoal, stir 1 hour, filtering, retain filtrate；
Under second step stirring, the mixed solution of 30ml ethanol and acetone is slowly added dropwise into filtrate, in the mixed solution, second
The volume ratio of alcohol and acetone is 1:1.
Under the stirring of 3rd step, solution is cooled to 10 DEG C with 5 DEG C of the speed of cooling per hour and kept, it is small to continue stirring 1
When；
4th step continues that solution is cooled into -8 DEG C with 5 DEG C of the speed of per hour cooling and kept, and 5ml50% is added into solution
Ethanol water, continue stirring 2 hours, be kept stirring for 55 turns per minute of speed；
4th step is filtered, and filter cake is washed three times with 50% ethanol water, uses about 5ml every time, and filter cake is spread out, done in 35 DEG C of vacuum
It is dry, bromocriptine methanesulfonate fine work is obtained, D50 is 26 microns, yield 90.38%, and high performance liquid chromatography detection purity is 99.79%.
Embodiment 2, first step 16g bromocriptine methanesulfonates crude product solution add 2.5g activity in 100ml absolute ethyl alcohols
Charcoal, stir 2 hours, filtering, retain filtrate；
Second step is slowly added dropwise the mixed solution of 60ml ethanol and acetone into filtrate, in the mixed solution, ethanol and acetone
Volume ratio be 3:1.
Under the stirring of 3rd step, solution is cooled to 10 DEG C with 5 DEG C of the speed of cooling per hour and kept, it is small to continue stirring 1
When；
4th step continues that solution is cooled into 0 DEG C with 5 DEG C of the speed of per hour cooling and kept, and 10ml50% is added into solution
Ethanol water, continue stirring 4 hours, be kept stirring for 50 turns per minute of speed；
4th step is filtered, and filter cake is washed three times with 50% ethanol water, uses about 8ml every time, and filter cake is spread out, done in 35 DEG C of vacuum
It is dry, bromocriptine methanesulfonate fine work is obtained, D50 is 48 microns, yield 91.46%, and high performance liquid chromatography detection purity is 99.92%.
Embodiment 3, first step 14g bromocriptine methanesulfonates crude product solution add 1.4g activity in 100ml absolute ethyl alcohols
Charcoal, stir 1.5 hours, filtering, retain filtrate；
Second step is slowly added dropwise the mixed solution of 50ml ethanol and acetone into filtrate, in the mixed solution, ethanol and acetone
Volume ratio be 2:1.
Under the stirring of 3rd step, solution is cooled to 10 DEG C with 5 DEG C of the speed of cooling per hour and kept, it is small to continue stirring 1
When；
4th step continues that solution is cooled into -4 DEG C with 5 DEG C of the speed of per hour cooling and kept, and 8ml50% is added into solution
Ethanol water, continue stirring 4 hours, be kept stirring for 55 turns per minute of speed；
4th step is filtered, and filter cake is washed with 50% ethanol water, and filter cake is spread out, and in 35 DEG C of vacuum drying, it is hidden to obtain methanesulfonic acid bromine
Booth fine work, D50 are 37 microns, yield 91.44%, and high performance liquid chromatography detection purity is 99.96%.
Claims (5)
1. a kind of D50 is the preparation method of the bromocriptine methanesulfonate of 26-48 microns, it is characterised in that is comprised the steps：
First step bromocriptine methanesulfonate dissolving crude product adds activated carbon in absolute ethyl alcohol, stirs 1-2 hours, filters, and retains
Filtrate；
Under second step stirring, the mixed solution of ethanol and acetone is slowly added dropwise into filtrate, the amount that mixed solution is added dropwise is first
Walk quantity of solvent 30-60%；
Under the stirring of 3rd step, solution is cooled to 10 DEG C with 5 DEG C of the speed of cooling per hour and kept, continue stirring 1 hour；
4th step continues that solution is cooled into -8 DEG C to 0 DEG C with 5 DEG C of the speed of per hour cooling and kept, and is added into solution
First step solvent volume 5-10% 50% ethanol water, continue to stir 2-4 hours, be kept stirring for speed 50-55 per minute and turn；
5th step is filtered, and filter cake is washed with 50% ethanol water, and filter cake is spread out, in 35 DEG C of vacuum drying.
2. according to the preparation method for the bromocriptine methanesulfonate that D50 described in claim 1 is 26-48 microns, it is characterised in that first
The concentration that solution prepared by step contains bromocriptine methanesulfonate is 8-16%（Mass volume ratio）.
3. according to the preparation method for the bromocriptine methanesulfonate that D50 described in claim 1 is 26-48 microns, it is characterised in that second
In the mixed solution for walking ethanol and acetone, the volume ratio of ethanol and acetone is（1-3）:1.
4. according to the preparation method for the bromocriptine methanesulfonate that D50 described in claim 1 is 26-48 microns, it is characterised in that second
The amount that step adds mixed solvent is the 38-54% of first step quantity of solvent.
5. according to the preparation method for the bromocriptine methanesulfonate that D50 described in claim 1 is 26-48 microns, it is characterised in that the 4th
The volume that step adds ethanol water is the 8% of first step quantity of solvent.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711170575.8A CN107814814A (en) | 2017-11-22 | 2017-11-22 | A kind of D50 is the preparation method of 26 48 microns of bromocriptine methanesulfonate |
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| CN201711170575.8A CN107814814A (en) | 2017-11-22 | 2017-11-22 | A kind of D50 is the preparation method of 26 48 microns of bromocriptine methanesulfonate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111965272A (en) * | 2020-07-29 | 2020-11-20 | 重庆智合生物医药有限公司 | High performance liquid chromatography analysis method of bromocriptine mesylate |
-
2017
- 2017-11-22 CN CN201711170575.8A patent/CN107814814A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111965272A (en) * | 2020-07-29 | 2020-11-20 | 重庆智合生物医药有限公司 | High performance liquid chromatography analysis method of bromocriptine mesylate |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180320 |
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| WW01 | Invention patent application withdrawn after publication |